The present invention relates to certain aryl-alkynoic, alkenoic and alkanoic acids and derivatives and their use in pharmaceutical compositions and in methods of treating inflammation, allergy and hyperproliferative skin disease.
European published patent Application No. 0 110 405 discloses compounds of the formula ##STR1## and pharmaceutically accepted salts thereof, wherein R.sub.1 and R.sub.2 are independently hydrogen, alkyl, carboxy, alkanoyloxy, aroyloxy, carboxyalkyl, carbalkoxyalkyl, carbalkoxy, alkanoyl, formyl, nitrile, amino, aminoalkyl, alkylamino, carboxamide, halo, trihalomethyl, hydroxy, aryloxy, nitro, sulfamyl, thio, alkylthio, and R1 and R.sub.2 when taken together with the carbon atoms to which they are attached form a phenyl ring;
Z is C or N, PA0 X is --0--, S--, NR.sub.4, --CH.sub.2 Z.sub.1 --, --CH.dbd.N--, --CH.dbd.CH--, --C.tbd.C--, --C.dbd.O, --CH.sub.2 ZCH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 CHR.sub.5 -- or --CH(C(R.sub.5).sub.3).sub.2 -- when R.sub.3 is monovalent or --C--CH.sub.2 -- when R.sub.3 is O; PA0 R.sub.3 is O, OH, OR.sub.4, SH, SR.sub.4, NH.sub.2, HNR.sub.4 or N(R.sub.4).sub.2 ; and PA0 m is an integer from 0 to 10; wherein Z.sub.1 is O, S or NR.sub.4 ; R.sub.4 is H, alkyl, pyranyl or aryl; and R.sub.5 is H or alkylfluoro. These compounds are said to have antiinflammatory and antiallergic activities. PA0 N is --CH.sub.2 --, --C(O)--, --CH(OH)-- or --CH(OR)-- PA0 Y is --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 S--, --SCH.sub.2, --CH.sub.2 --N(R.sup.2)--, --N(R.sup.2)--CH.sub.2 --, --C(O)--N(R.sup.2)--, --N(R.sup.2)--C(O)--, --O--, --S-- or --N--; PA0 Q is Z--(CH.sub.2).sub.n --C(A)--B; ##STR3## m is 0-6; n is 0-6; PA0 p is 1-3; PA0 A is O or S; PA0 B is OR.sup.2, SR.sup.2 or N(R.sup.2).sub.2 ; PA0 R.sup.1 is hydrogen, loweralkyl, loweralkoxy or halo; PA0 R.sup.2 is hydrogen or lowerlakyl; and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated nasobronchial obstructive air passageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like. PA0 m represents an integer of from 0 to 4; PA0 n represents an integer of from 2 to 6: PA0 Ar represents ##STR4## p is 0, 1 or 2; X represents --C.tbd.C--, --CH.dbd.CH-- or --CH.sub.2 --CH.sub.2 -- PA0 Y represents O, S, NR.sup.7 or a covalent bond; PA0 R.sup.1 represents alkoxy, OH or N(R.sup.7).sub.2 ; PA0 each R.sup.2 independently represents a substituent selected from halo, alkyl, alkoxy, CN, OH, NO.sub.2, CF.sub.3 or cycloalkyl; PA0 R.sup.3 represents H, alkyl, alkenyl, alkynyl, alkoxy, or alkylthio, with the proviso that if Y is O, S or NR.sup.7, R.sup.3 is not alkoxy or alkylthio on the carbon atom adjacent to Y; PA0 R.sup.4 represents H, alkyl, alkenyl, alkynyl or a cyclic group selected from: ##STR5## wherein Z.sup.1 is N, CH or CR.sup.2, Z.sup.2 is CHR.sup.7, O, S or NR.sup.7 and Z.sup.3 represents NR.sup.7, S or O; PA0 R.sup.5 and R.sup.6 may be the same or different and each independently represents H, alkyl, alkoxy, or alkylthio, with the proviso that R.sup.5 and R.sup.6 are not both alkoxy and/or alkylthio on the same carbon atom; and PA0 each R.sup.7 is independently selected from H or alkyl. Thus, the invention also includes the use of the compound of formula I in pharmaceutical compositions in combination with a pharmaceutically acceptable carrier and in methods of treating mammals for allergy, inflammation and hyperproliferative skin disease.
Blythin U.S. Pat. No. 4,405,810 discloses certain 7-arylhept-5-ynoic acids and derivatives thereof and indicates that such compounds have antiallergy and antiinflammatory activities.
Musser et al. U.S. Pat. No. 4,528,392 discloses compounds of the formula ##STR2## wherein X is OR.sup.2, SR.sup.2, N(R.sup.2).sub.2 or halo;